Hyponatremia associated with high urine osmolality is usually caused by inappropriate secretion of antidiuretic hormone. However, secondary hypoadrenalism is also accompanied by hyponatremia and with features indistinguishable from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). As secondary hypoadrenalism requires a specific treatment, a high index of suspicion and appropriate hormonal testing are required to differentiate between these two entities. We retrospectively studied 10 patients with a previously undiagnosed hypothalamic-pituitary disease who presented with an acute symptomatic hyponatremia. Mean age (+/-SD) was 65.1+/-8.4 yr. Mean serum sodium was 120.7+/-2.9 nmol/l and urinary osmolality, 453.9+/-74 mosmol/kg. Serum creatinine, urea and uric acid were low. Mean serum morning cortisol was low, 104.0+/-55.2 nmol/l. High-dose ACTH test showed adequate increment of serum cortisol in 3 out of 7 patients tested. Two of these 3 patients did not respond adequately to the low-dose ACTH test. Endocrine evaluation disclosed partial or complete hypopituitarism in all 10 patients. Six patients had pituitary macroadenomas, one had a craniopharyngioma, one patient had a large aneurysm of the internal carotid with sellar destruction and two others had empty sella. Treatment by fluid restriction did not affect serum sodium levels significantly. In contrast, all patients achieved normal sodium when treated by glucocorticosteroid. Central hypoadrenalism should be considered in any patient presenting with hyponatremia with high urine osmolality. Low-dose ACTH test should be performed and followed by appropriate endocrine and imaging studies. Hyponatremia in these patients is promptly corrected by glucocorticosteroid replacement.